WO2007128533A2

WO2007128533A2 - Device and method for examining and evaluating a biologically active and/or activatable substance

Info

Publication number: WO2007128533A2
Application number: PCT/EP2007/003976
Authority: WO
Inventors: Jahn Wolfgang
Original assignee: Mevitec Gmbh
Priority date: 2006-05-05
Filing date: 2007-05-04
Publication date: 2007-11-15
Also published as: DE202006012071U1; WO2007128533A3; DE102006021343A1

Abstract

The invention relates to a device and method for the optical examination and evaluation of a biologically active and/or activatable substance (2) by applying infrared, visible or ultraviolet light. The substance to be examined or evaluated is optically excited so that it either emits light (in particular fluorescence analysis) or modifies the wavelength of the applied light (particularly Raman analysis). According to the invention, the device comprises a measuring surface section (11) on its upper or outer side, whose shape and dimension are adapted to the biologically active and/or activatable substance (2).

Description

Device and method for the examination and evaluation of a biologically active and / or activatable substance

The invention relates to a device and a method for the optical examination and evaluation of a biologically active and / or biologically activatable substance, in particular of a human or animal body tissue, by the application of infrared, visible or ultraviolet light, in which the substance under investigation so it is optically excited that it emits light (fluorescence analysis) or changes the wavelength of the incident light (Raman analysis).

Human (or animal) metabolism is the sum of all life-sustaining biochemical and biophysical ones

Processes. The metabolism differs from person to person as well as from one stage of life to the next, as well as many other factors such as physical stress, illness and stress. With the help of metabolic analyzes, comprehensive information about the current state of health of the human organism can be obtained. So far, only the results of different individual examinations are used in the metabolic analysis. These include, in particular, laboratory analyzes of organ activities, of the immune system, of the hormone system, of lipid metabolism, of mineral metabolism, etc., such investigations being costly and, above all, very time-consuming. For metabolic analysis, the collection and analysis of blood samples is still common, and these must be sent to a laboratory for analysis. Apart from the costs, they have further significant disadvantages. Due to the necessary transport and the long duration of the examination, changes in blood samples can occur which considerably affect the result, for example by freezing or by oxidation effects. In addition, blood collection is uncomfortable for the patient and sometimes even dangerous. In addition, various spectrometers for the optical examination of the fluorescence properties of biological tissue samples are known in the prior art. Proteins in the biological tissue are intrinsically fluorescent in various species, such as porphyrin, aromatic amino acids such as tryptophan, tyrcsin, phenylalanine, and the like. A disadvantage of the known investigation method, it is again that the biological tissue samples taken from the subject and for optical examination in a

Cuvette or on a sample carrier must be attached. The previous examination procedures take place in the laboratory and are not suitable for immediate, rapid examinations of the subject on site or in the immediate working or leisure environment of the subject. In addition, the methods used so far are invasive, d. H. connected with an engagement in the body portion.

The invention is based on the object, an apparatus and a method for optical examination and especially

Evaluation of a biologically active and / or biologically activatable substance, in particular of a human or animal body tissue, in particular with regard to the substances of the cellular metabolism to provide, with which or a simple, i. can be ensured by the subject itself, immediate, rapid examination of the subject can be guaranteed, on site or in the immediate working or leisure environment of the subject, the device or the method in addition to the mere examination beyond a medically sound, reproducible overall assessment of the organism which belongs to the substance under investigation, guaranteed or at least opened.

The object is achieved by the device specified in claim 1 and the method specified in claim 12. The device according to the invention has a light source which can be operated with electrical energy, an optical light guide, with which the light emitted by the light source can be supplied as radiation of the substance to be examined, an optical or optoelectronic sensor device associated with the substance to be examined, which transmits the biologically active and or the biologically activatable substance emitted or detected by the changed light, and one of the sensor device associated optical or optelektr- lektronische spectrometer on which emitted by the substance under examination or in its wavelength changed light with respect to the intensity of the light at at least one frequency or with respect to the frequency shift, wherein a corresponding measurement signal is output to an evaluation circuit associated with the spectrometer device, and is characterized in that the device is located on its upper side side or on its outer side has a measuring surface section, which is adapted in shape and extent of the biologically active and / or biologically activatable substance to be examined.

Following the principle of the invention, the biologically active and / or biologically activatable substance is a biological tissue, ie a human, animal or plant tissue. In principle, an application of the invention to other, not necessarily living matter would be conceivable, for example, to measure biologically relevant factors in a soil substance or humus, or other, under the term biologically activated substances falling, such. As nutrient or sugar solutions, and the like.

The invention makes possible a noninvasive optical examination of a biologically active and / or biologically activatable substance, in particular tissue material of a test person; no tissue samples have to be taken or inserted or clamped in measuring probes or the like. Characterized in that the light exit section of the optical Light guide and the sensor device form a structural unit, and this structural unit has on its upper side or outside a measuring surface portion which is adapted in shape and extent to be examined human or animal biological tissue, the optical examination of the substance to be measured simply by suc ^{In this} way, the measuring surface section is brought into contact with the skin at or touching the skin surface of the test person so as to contact the skin and is held at this point for the duration of the measuring process, which is usually a few seconds. With the invention succeeds an easy to be carried out, ie by the subject itself feasible, immediate, rapid examination, on site or in the immediate working or leisure environment of the subject.

With the device according to the invention, an examination and, above all, an evaluation of the biological tissue immediately following the examination is possible within a few seconds, and on the basis of this noninvasive metabolic analysis, the immediate presentation or display of the current overall health or state of health the subject can be guaranteed. With the method according to the invention or the device according to the invention, a representation of the current overall condition of a subject is thus possible, which can already provide the physician with important basic information on medically relevant features of the patient.

The device according to the invention works by measuring the autofluorescence of the body's own metabolite substances in the interior, which was excited by means of radiation, in particular in the short-wave UV range or in the near UV range. The advantages of the device according to the invention, in addition to the bloodless, non-invasive analysis method, are, above all, the measurement and evaluation lasting only a few seconds, so that, for the first time, a cost-effective monitoring of the metabolic regulation can be carried out. lation without compromising the patient is possible. The autofluorescence of cells, tissues and substances is based on the stimulation of endogenous fluorofore. Important endogenous fluorophores include tryptophan, the coenzymes NADH, NADPH and flavins, as well as zinc-containing and metal-free porphyrins. In medicine, this phenomenon can be used for diagnostics, for example for the early detection of malignant cell changes on the skin and in the mucous membranes of the hollow organs. The measurement of metabolic products dissolved in the interstitium is medically relevant and extremely informative. Interstitium is the fluid-filled space between the cells that is filled with connective tissue, nerves and blood vessels and is in constant contact with the cells, blood vessels and lymphatic system. The interstitium is responsible for the transport of nutrients to the cells and the metabolites of the cells as well as the signaling substances between the cells. Changes in cell metabolism or impaired cell functions affect the composition of the interstitial fluid in a specific manner. For this reason, the interstitium is well suited to measure both transient changes in cellular metabolism through physical or mental stress, as well as metabolic disorders due to organ damage or disease.

The autofluorescence values measured with the device according to the invention or the method according to the invention are combined with one another in a specific manner and then make it possible to make statements about existing metabolic disorders, the influence of stress or other regulatory disorders, and thus provide information about the current state of health of the subject , The determined parameters allow the following statements on the current state of health: metabolism regulation, protection against hyperacidity, immune defense, connective tissue condition, regulation of inflammatory processes, protection against oxidative stress, mental resilience, allergic activation, protection against infectious processes, cellular renewal education processes, cell degradation processes and the current micronutrient requirement. Finally, the invention makes it possible to produce reproducible, medically sound statements about the general metabolic activity, its regulation and the influence of inflammations, allergies, viral or bacterial

Infections, etc. in a relatively straightforward way to allow. In addition, the invention opens up a wide field of application of light-induced autofluorescence of the body's own substances.

In the following, the achievable with the method according to the invention or with the device according to the invention statements are explained in more detail. Protection against acidification: Acidification takes place where a metabolic process takes place intensively and the acids accumulating during the metabolism are not sufficiently broken down. The entire metabolism is based on acid production, all metabolic intermediates are acids that have to be buffered or bound in various ways, for example. The so-called hyperacidity takes place mainly in the intestine (during the metabolism). If there is an excess of acids and thus a shift in the pH level, especially the enzyme activity is disturbed, which can lead to metabolic disorders to the severest inflammation, unstable immune system and diseases. Values with a tendency to "red

Therefore, "area" often indicates the risk of acidification, which can lead to permanent inflammation, poor skin appearance, diarrhea and constipation, and even autoimmune diseases Immune defenses: This parameter provides information about how intensively the organism provides antibodies to itself The more the measured values lie in the "red value range", the higher is the risk of overstraining the immune system, ie the organism is no longer able to defend itself adequately enough, so that various diseases occur Metabolic regulation: This states how the organism is able to break down and destroy nutrients. values, and to ensure the maintenance of one's own bodily functions (growth, warmth, regeneration, immune activations, etc.). The more clearly the values measured with the invention are in the "red range", the more likely is the restriction of the performance or restrictions of all body and immune functions.

/ -> π r »R i n H pnDwoh Q 7 n c 1" a n H • R ϊ n H orrowoho ϊ σ + "a l T o σ τ» τ a σ n n c n rα

Structure, holding our body together, i. Collagen and elastic fibers, ligaments, tendons and fibers in the subcutaneous tissue, ie everything that connects other tissues. The more the corresponding values are in the "red" range, the higher the risk that the maintenance of a certain proportion of elastic and collag- nous portions, which are important for a state of tension and the normal reaction of the musculature, is disturbed , This can lead to loose tissue, impaired mobility (joint functions) and even to diseases such as arthrosis, arthritis, etc. Regulation of Inflammatory Processes: Inflammation is a life-long process that must be ongoing and expired, as it is part of the normal regulation of metabolism, immune functions and enzyme functions, unless they are chronic events. The more the values measured according to the invention are in the "red zone", the higher is the probability that chronic inflammations can occur which can lead to the disturbance of vital functions. Protection against oxidative stress: the oxidative protection includes all substances that are able to absorb oxidative stress (free radicals), which are the so-called antioxidants. The organism is dependent on oxygen in its existence, because it enables the production of energy from the

Nutrition to maintain all bodily functions, on the other hand, the oxygen also has a destructive effect, since it can lead to the formation of oxygen species, so-called radicals, which are highly aggressive and destructive during the degradation of food. Normally, a healthy organism can absorb this burden, but this natural burden may be increased by one unhealthy lifestyles and health-critical living conditions such as physical and psychological pressure to work, stimulants and drug use, environmental toxic influences, changing dietary habits, and the like. As a result, there is an excess of free radicals that is not adequately protected, and oxidative stress can result. Meanwhile, it is known that 70% of all diseases are caused by oxidative stress. Permanent protection or sufficient supply of antioxidants is therefore a prerequisite for the existence of every organism. The more the corresponding values in the "red area", the higher the risk for oxidative stress, since there is no sufficient supply of antioxidants. Mental Resilience: This is the ability to think, to turn thinking into will, and to control the will so that the body does what one wants. Allergic Activation: Allergies in a healthy context is the fight of the immune system against all foreign substances that arise in or enter the body. Similar to inflammations, allergies in the organism are permanently eliminated and are vital for survival. But if it comes to an overreaction, the known allergy symptoms arise. The more the measured values are in the "red zone", the stronger is the overreaction of the immune system, or in other words, the faster the overreaction subsides, the better is the immune regulation. Protection against infectious processes: This statement does not mean how great the protection is, in order not to get infections, because just like inflammations and allergic reactions, infections must always occur in order to be viable. The shorter the duration of the infectious symptoms, the higher the protection, ie the early containment, so that an infection is not unnecessarily burdened by the organism. The worse the measured values, the higher the risk that an infectious process becomes a more serious infection. New cell regeneration processes: These involve many physiological and pathological processes, therefore, in the case of According to the invention, only a coarser orientation is possible with regard to these parameters, whether it is a negative new cell formation or an only increased cell regeneration in the context of regeneration processes. It is important that cell neoformation is always to be considered in the context of cell degradation. If the balance between cell structure and cell degradation disturbed, the cause must be examined in a differentiated physician. Cell degradation processes: Again, this parameter merely gives a coarser orientation, and states whether there is an increased cell efflux. It is also important here to always consider the formation of new cells in connection with cell degeneration. General Performance: This is a summary statement that arises from factors such as immune defense, substance turnover regulation, oxidative stress, etc., as well as factors such as sleep recovery and the like. Training state: This is the ability of the organism to counteract any radical stress. The more the values in the "red area", the less the organism is protected from radicals, ie it is less resilient.

The device according to the invention operates in such a way that, by placing or applying a human or animal body part on the sensor device, a plurality of substances capable of fluorescence in the tissue fluid are excited by a light pulse emitted by the light source, and these substances themselves now have light components in response thereto transmit this fluorescence light computer-aided and the fluorescence values of these analyzed parameters are calculated in relation to each other. From the optical examination or analysis of the biologically active and / or biologically activatable substance then several different metabolic parameters can be determined, these specific metabolic parameters cell division activity and / or metabolic activity and / or the activity of biosyntheses and / or the Regulation of immune functions and / or inflammatory processes and / or energy expenditure and / or energy consumption for cell division activity and / or regulated and unregulated cell regeneration and / or inflammatory regulated cell regeneration processes and / or risk parameters of injury and / or risk parameter activated tissue regeneration and / or have the complex Stoffwβch- Seicharakteristik and / or the redox equivalent and / or the mental stability parameter.

Following the principle of the invention, it can be provided that at least part of the optical light guide and the sensor device are accommodated in a housing, and on or in the upper side of the housing, a bearing surface section is provided or provided which comprises the measuring surface section or at least partially correlates on which a body part of the subject corresponding to the substance to be examined, in particular a hand, a forearm or a foot or a leg, is placed, wherein the support surface portion formed on or in the top of the housing guide means for aligning the be deposited on the support surface portion Body part of the subject is provided.

According to a preferred embodiment of the invention can be provided that the optical light guide has a light exit portion, which forms a structural unit with the sensor device, said structural unit has on its upper side or outside the measuring surface portion. In this case, the guide device can be formed by a depression or thickening, which is provided on or in the upper side of the housing and has approximately medium finger widths.

Following the principle of the invention, the optical examination is carried out on an unclothed or easily exposed part of the body of the skin surface of the hand, arm, foot, leg or face or the neck and upper part of the skin. the shoulder of the subject. According to the invention, therefore, the surface of the measuring surface portion is approximately convexly curved and formed substantially the contours of such a body part, for example, the slightly clenched hand, following. Advantageously, the light source, the optical light guide, the sensor device, and the Spektrometεreinrichtung housed in a housing, and on or in the top of the housing is a measuring surface portion comprehensive or at least partially correlated bearing surface section is formed or provided on which a corresponding to the biological tissue to be examined body part of the subject, in particular a hand, a forearm or a foot or a leg is placed, wherein the support surface portion formed on or in the top of the housing guide means for aligning the ablated on the support surface body part of the subject can be provided.

In a further preferred embodiment of the invention, the surface of the measuring surface section is strongly convexly curved and formed substantially following the contours of a clenched hand. In this case, the measuring surface portion may be formed as part of the surface of a handlebar or steering wheel, or a steering wheel, or a joystick, or other steering or control device of a land, water or aircraft or spacecraft. The advantage of this training is, in particular, to examine the driver of a vehicle, such as truck drivers, skippers or pilots, who have a special responsibility in terms of alertness and concentration, during the exercise of his medical or biological activity, in case of disruption, for example Fatigue in the driver to be able to take appropriate countermeasures. The invention thus succeeds in the installation of a fuse of the driver against falling asleep in the vehicle, whereby accidents caused in this way can be avoided.

In a further preferred embodiment of the invention, an image display device is formed on the measuring surface section or in the immediate vicinity thereof, on which both the measurement results are displayed, and a menu-driven software program for controlling the device according to the invention is displayed.

The optical spectrometer device according to the invention may comprise a grating spectrometer, or a Fourier transform spectrometer or a filter spectrometer. In a grating spectrometer, the diffraction of the light radiation on a grating is used for its dispersion. The scanning of the spectrum is carried out either by rotating the grating, whereby temporally different wavelengths are detected by a point detector, or by a fixed grid, wherein the spectrum in the desired wavelength range is recorded by an arrow detector. A Fourier transform spectrometer is characterized in that an interferometric filter is tuned, and the tuning is recorded in a so-called interferogram. The wanted spectrum is then obtained by Fourier transform of the interferogram in the desired wave vector range. Filter spectrometers are based on a filter disk, which select the individual wavelengths. Filter spectrometers generally have the two disadvantages that on the one hand a good filter disk can only be produced by very expensive coating techniques, and on the other hand that the light to be analyzed passes through the filter disk, as a result of which a lot of light is lost and a poor signal-to-noise ratio is produced. Because of a structurally simple construction and a very good wavelength resolution, the grating spectrometer is given preference in the embodiment according to the invention. A miniaturization of the device according to the invention can take place if, according to a further embodiment of the invention, the optical or optoelectronic spectrometer device associated with the sensor device has a semiconductor sensor device which has at least one avalanche photodiode with a semiconductor gate, which corresponds to the frequency to be measured. FrcQcπzvcrscuicuuπy sntspncut. The semiconductor sensor device may have a frequency gap which can be varied with respect to the measurement frequency and / or can be tuned.

The method according to the invention is characterized by the following steps:

Irradiating the substance to be examined with a light emitted by a light source, which is supplied to the substance to be examined by means of an optical light guide,

Detecting the radiation emitted or changed by the substance by means of an optical or optoelectronic sensor device assigned to the substance to be examined,

Measurement of the light emitted by the examined substance or changed in its wavelength with regard to the intensity of the light at at least one frequency or with respect to the frequency shift by means of an optical or optoelectronic spectrometer device associated with the sensor device, and

Output of a corresponding measurement signal to an evaluation circuit.

Here, the biologically active and / or biologically activatable substance is in particular a biological tissue, ie a human, animal or plant tissue.

Following the principle of the method according to the invention, it is provided that by applying or applying the biologically active and / or biologically activatable substance on the sensor device several substances capable of fluorescence n, m (n, m = a, b, c, d,...) are excited in the substance by a light pulse emitted by the light source, and these substances a, b, c, d, ... in response to this, emit itself light signals of a certain wavelength and in a certain intensity, these light signals are measured.

In this case, from the measured intensity values (I _a , I _b , I _c , I _d ) of the light signals a plurality, at least three or four, in particular at least five or six different metabolic parameters S _n (where n = a, b, c, d , ...), where: S _n ⁼ F (I _n , λ _n ) X G (I _m , λ _m ); where F and G are two different mathematical functions of intensities and wavelengths, with n, m = a, b, c, d, ..., and n ≠ m; and the correlation or mathematical combination X of the two functions F and G in the simplest form is a product or a sum, in the form: S _n = π [F (I _n , λ ") • G (I _n , λ _m )] or S _n = Σ [F (I _n , λ ")] G (I _m , λ j], where n, m = a, b, c, d, ..., and n ≠ m, or n = m.

The substances n, m with their measured emission wavelengths (λ _n , λ _m ) and their measured intensities (I _n , I _m ) have in particular the following biochemical substances:

a = ATP (adenosine triphosphate), and / or b = GTP (guanosine triphosphate), and / or c = FAD (flavin adenine dinucleotide), and / or d = NADH (nicotinamide adenine dinucleotide reduced), and / or e = NADP (nicotinamide adenine dinucleotide phosphate), and / or f = kynurenine, and / or g = -Or-o-t-acid, and / or T "h = thromboxane, and / or i = tryptophan. The fluorescence intensities (I _n , Im) are in the wavelength range (λ _n , λ _m ) from 287 nm to 800 nm, preferably from 340 nm to 600 nm, for the substances n, m = a, b, c, d, .. measured.

If a measurement of the fluorescence intensities (I _n , Im) takes place at a defined point in time (t _n , t _m ) and / or at defined time intervals (Δt _n , Δt _m ), where: n ≠ m, t "≠ t" Δt "≠ Δt" so different control and regulation processes can be revealed by these course measurements.

If at a defined time (t _n , t _m ) of the measurement a psychological or physical stress of the patient takes place, and the fluorescence intensities (I _n , I _m ) are measured several times before and after exercise, so beyond the regulatory process in the metabolism be determined.

From the optical examination or analysis of the biologically active and / or biologically activatable substance and from the measurement of the metabolic parameters S _n (with n = a, b, c, d,...), Several different specific state variables Z _{n are used} as mathematical functions of the Metabolic parameters S _{n are} calculated and graphically represented, these specific state variables Z _n having the following:

α = cell division activity, and / or β = metabolic activity, and / or

Y = activity of biosyntheses, and / or δ = regulation of immune functions, and / or ε = inflammatory processes, and / or ζ = energy turnover, and / or η = energy consumption for cell division activity, and / or θ = regulated and unregulated cell regeneration, and / or ξ = inflammatory regulated re-growth processes, and / or p = risk parameter of damage to health, and / or σ = activated tissue regeneration, and / or φ = complex metabolic characteristic, and / or X = redox equivalent, and / or ψ = mental stability parameter.

In particular, the method according to the invention can be used for the noninvasive examination of control and regulating processes of human and animal metabolism, and / or for the diagnosis of diseases and preventive examinations, and / or for routine examinations of occupational groups and athletes with high physical and psychological stress, and / or be used for therapy control, and / or the course of dialysis and apheresis treatment as well as for the determination of the antioxidant requirement.

In a preferred embodiment of the method according to the invention, fluorescence intensities are measured in the wavelength range from about 287 nm to about 800 nm, preferably from 340 nm to 600 nm, in particular for metabolically relevant substances with predetermined emission wavelengths, preferably ATP, GTP, FAD, NADH, NADP, Kynurenine, orotic acid, thromboxane and tryptophan.

Of advantage are biologically active materials, the one

Autofluorescence excited in the cellular and intercellular region with light having an excitation wavelength of 287 nm to 340 nm, preferably 340 nm for emission.

Advantageous developments of the invention are specified in the subclaims.

Further advantages and expediencies will become apparent from the following description of exemplary embodiments with reference to the drawing. It shows: Figure 1 is a schematic view of an inventive

Device according to a first embodiment; Figure 2 is an isometric view of the first

Embodiment; Figure 3 is a sectional view of the first

Embodiment; Figure 4 is an overall view of the first

Embodiment; Figure 5 is an overall view of the first embodiment with an attached hand; Figure 6 is an overall view of a second

Embodiment; Figure 7 is a schematic sectional view of the optical

Light guide with the light exit section; Figure 8 is a schematic sectional view of the human

Skin surface for explaining the measuring method according to the invention; Figure 9 is an overall view of a third

Embodiment; Figure 10 is an overall view of the third

Embodiment with an attached hand; and FIG. 11 shows a schematic screen representation of the specific state variables Z _n determined by the method according to the invention.

In the figures, embodiments of the invention are shown, wherein like reference numerals designate like components.

The figures show a device 1 for the optical examination or analysis of a biologically active and / or biologically activatable substance 2 by the application of infrared, visible or ultraviolet light, in which the examined material 2 is optically excited so that it emits light (fluorescence analysis) or the wavelength of the incident light changes (Raman analysis). The device 1 has a light source which can be operated with electrical energy 3, an optical light guide 4, with which the light emitted by the light source 3 as radiation to be examined human or animal biological tissue 2 can be fed, a the human or animal biological tissue to be examined 2 associated optical or optoelectronic sensor device 5, which the detects radiation emitted by the biological tissue, an optical or optoelectronic spectrometer device 6 associated with the sensor device 5 with which the light emitted by the material under investigation or changed in its wavelength and coupled out via an optical waveguide 15 is measured with respect to the intensity of the light at at least one frequency or the frequency shift is, with a corresponding measurement signal via a USB cable 7 to a (not shown) evaluation circuit of an external computer is output. According to the invention, the light exit section 8 of the optical light guide 4 and the sensor device 5 form a structural unit 9; this structural unit 9 has on its upper side 10 or outer side a measuring surface section 11, which is adapted in shape and extent to the human or animal biological tissue 2 to be examined.

In the first exemplary embodiment of the invention shown in FIGS. 1 to 5, the surface of the measuring surface section 11 is approximately convexly curved and essentially follows the contours of a slightly clenched hand. Here, the light source 3, the optical light guide 4, the sensor device 5, and the spectro- meter device 6 housed in a housing 12, and on or in the top of the housing 12 is a measuring surface portion 11 comprehensive or at least partially correlating bearing surface portion 13 is formed or provided on which a body part of the test person, in particular a hand, corresponding to the human or animal biological tissue 2 to be examined is placed, wherein the support surface section 13 is one on or in the upper side of the housing 12 formed guide means 14 for aligning the ablated on the support surface portion 13 body part of the subject is provided. The guide device 14 is formed in the illustrated embodiment by a provided on or in the top of the housing 12, approximately middle finger wide recess.

In the second exemplary embodiment of the invention shown in FIG. 6, the surface of the measuring surface section 11 is strongly convexly curved and essentially follows the contours of a clenched hand. In this embodiment, the measuring surface portion 11 may be formed as part of the surface of a car steering wheel 16, or a steering wheel, or a joystick, or other steering or control device of a land, water or aircraft or spacecraft. The steering wheel 16 also forms the housing 12 of the device 1 according to the invention.

In the case of the third exemplary embodiment of the invention illustrated in FIGS. 9 and 10, the surface of the measuring surface section 11 is formed essentially following the contours of a slightly clenched hand. On or in the upper side of the housing 12, in turn, a bearing surface section 13 which encompasses the measuring surface section 11 or at least partially is designed or provided on which the human or animal biological tissue 2 to be examined is placed on the corresponding body part of the test subject, in particular a hand is provided, wherein the support surface portion 13 is provided on or in the top of the housing 12 formed guide means 14 for aligning the bearing on the support surface portion 13 body portion of the subject. In addition, the edge portions 14a of the housing 12 are rounded, and also serve to guide the hand 2. In the third embodiment according to Figures 9 and 10 is the

Housing 12 with respect to the illustrated in Figures 1 to 3 first embodiment of the invention structurally essential smaller dimensioned / it can be provided in the third embodiment, that the light source 3 and the spectrometer 6 are housed in a separate component from the housing 12, said accommodated in the separate component optical and optoelectronic components via the optical light guide 4 with the in the housing 12 accommodated sensor device 5 are connected. In the third exemplary embodiment, an image reproduction device 17 is formed on the measuring surface section 11 or in the immediate vicinity thereof, for example in the form of a miniature screen 17 integrated in the housing 12. In addition to the image reproduction device 17, function keys 18 are formed, with which the information displayed on the display 17 displayed measuring method can be controlled.

FIG. 8 schematically shows the anatomy of the skin for explaining the analysis method according to the invention. The organ of the human (or animal) skin, for example, consists of three interconnected but tissue-different layers, with the outermost

Layer 20 is referred to as epidermis (epidermis), the middle layer 21 as corium (dermis), and the bottom layer 22 as subcutis (subcutis). The epidermis 20 is the vascularized outer layer of the skin, which in turn is divided into sublayers. The uppermost layer of the epidermis is the cornea (stratum corneum), on which the light guide is placed. About five to seven percent of the incident light 23 is remitted at this layer 20 a. The epidermis 20 is followed by the corium (dermis) 21. It gives the skin its tear resistance and its deformability. This is followed by the subcutis 22, which is loosely connected to the underlying muscle fibers. It is composed of connective tissue and serves, among other things, as fat storage. Between epidermis 20 and corium 21 there is a network of arterioles and venules (plexus), which ensure the supply of the skin cells. The penetrating light 23 is applied to the cellular structures of the different layers. scattered and absorbed through the skin pigments, bilirubin, the oxygenated and deoxygenated hemoglobin. The skin tissue thus consists of different cell types, and is traversed by the smallest muscle-free blood vessels (capillaries) that connect the venules (small veins) and the arterioles (small arteries). In the capillaries of the outward transfer of substances will exchange (such as electrolytes) and the gas exchange (O _2, CO ₂₎ between blood and tissue instead. Arteries, veins and capillaries form the transport system in the body, which enables the supply of oxygen and other nutrients to body organs and body tissue as well as the removal of oxygen-poor blood and metabolic products. The method according to the invention is based on the measurement of the autofluorescence of endogenous metabolic substances 24 in the interstitium, which are excited by means of the radiation 23, in particular in the short-wave UV range or near UV range, and by intrinsic or intrinsic. Autofluorescence of cells, tissues and substances due to the excitation of endogenous fluorophores reemit specific light beams 25 with different wavelengths, which are detected by the sensor device 5 according to the invention and evaluated.

Several substances n, m (n, m = a, b, c, d,...) Capable of fluorescence in the substance 2 are excited by a light pulse 23 emitted by the light source, and these substances a, b, c , d, ... send in response to light signals of a certain wavelength and in a certain intensity, these light signals are measured. In this case, from the measured intensity values (I _a , Ib _/ I _c , I _d ) of the light signals a plurality, at least three or four, in particular at least five or six different metabolic parameters S _n (where n = a, b, c, d, ...), where: S _n = F (I _n , λ _n ) XG (I _m , λ _m ); where F and G are two different mathematical functions of intensities and wavelengths, with n, m = a, b, c, d, ..., and n ≠ m; and the correlation or mathematical combination X of the two functions F and G in the one is a product or a sum, in the form: S _n = fl [F (I _n , λ ") • G (I _m , λ _m )] or

S _n = Σ [F (I _n , λ _n ) G (I ₁₁₁ , λ _m )], where n, m = a, b, c, d, ..., and n ≠ m, or n = m ,

The substances n, m with their measured emission wavelengths (λ _n , λ _m ) and their measured intensities (I _n , I _m ) have in particular the following biochemical substances: a = ATP (adenosine triphosphate), b = GTP (guanosine triphosphate), c = FAD (flavin adenine dinucleotide), d = NADH (nicotinamide adenine indinucleotide reduced), e = NADP (nicotinamide adenine dinucleotide phosphate), f = kynurenine, g = orotic acid, h = thromboxane, i = tryptophan.

From the optical examination or analysis of the biologically active and / or biologically activatable substance and from the measurement of the metabolic parameters S _n (with n = a, b, c, d,...), Several different specific state variables Z _{n are used} as mathematical functions of the Metabolic parameters S _{n are} calculated and graphically represented, these specific state variables Z _n having the following values (see FIG.

α = cell division activity, d. H. a statement as to whether regulated or unregulated cell replication is taking place and, in particular, to what extent the activity of cell regeneration is occurring (normal or disturbed).

ß = metabolic activity, states how the regulation of the metabolic rate, ie the assembly and disassembly, or the utilization of food and nutrients expires. If this is disturbed, fermentation proportions may be activated or the glucose is re-formed mainly by protein degradation. The enrichment of various metabolic products can endanger the organism. It causes damage to the metabolism, which can cause all kinds of diseases. Y = activity of biosynthesis, includes all synthesis processes (= developmental processes), which take place in life, ie the maintenance metabolism with the permanent rebuilding and building of cells. In case of limited activity disturbances in the area of the maintenance of the body substance, eg. As the wound healing, immunoreactivation, etc. So all necessary for the renewal of the body structure processes.

δ = regulation of immune functions, says how effectively the immune system works against pathogens of all kinds.

ε = inflammatory processes, d. H. It is measured whether inflammatory processes are currently taking place in the body.

ζ = energy turnover, it is measured how the energy gained from the food is used, consumed or converted, that is used, eg. For example, for growth, heat production, organ activities, etc., thus expressing how the body is able to produce chemically bound energy from food and then provide it.

η = energy expenditure for cell division activity, is a part of the energy expenditure needed for the renewal or reproduction of the cells. If this value is in the red, this means an increased destruction of cells, which should actually be regenerated.

θ = regulated and unregulated cell regeneration, indicates in a manner similar to the above value how the relationship between cell assembly and degradation is, and how this may be disturbed.

ξ = inflammatory regulated new cell regeneration processes, this is a special statement on cell neoplasm in the context of immune activation in relation to inflammatory processes. p = risk parameter of damage to health, this is a summary statement that results from all other values.

σ = activated tissue regeneration, this is a specific statement on tissue regeneration, and a complementary value.

φ = complex metabolic characteristics, reflects everything that is involved in the metabolism.

χ = redox equivalent, or redox potential, reflects the measurement of redox regulation or redox changes. Statements are made on the possibility of oxidative stress and, above all, how much reductive capacity is being lost to the organism at the moment. It reproduces the relationship between oxidants and antioxidants and their perturbation, which ultimately suggests disturbed bioregulation.

These aforementioned specific state variables Z _n are shown as absolute value 26 and as color gradient 27 in the image display device 17, as shown schematically in FIG. 11. A "red" reading indicates increased activation of the regulatory process, which can be seen as negative as well as positive, for example, in a necessary activation in an infection. Therefore, it is important not to consider the measured values of the specific state variables Z _n individually, but in their entirety.

Claims

claims

1. A device for optical examination and evaluation of a biologically active and / or biologically activatable substance (2) by the application of infrared, visible or ultraviolet light, in which the substance under examination is optically excited so that it either emits light itself (in particular fluorescence analysis) or the wavelength of the applied light changes (in particular Raman analysis), the device comprising:

a light source (3) which can be operated with electrical energy,

- An optical light guide (4), with which the light emitted from the light source (3) can be supplied as radiation of the substance to be examined (2), - one of the substance to be examined (2) associated with optical or optoelectronic sensor device (5) the light emitted by or modified by the biologically active and / or biologically activatable substance (2) detects an optical or optoelectronic spectrometer device (6) assigned to the sensor device (5), with which the substance emitted by the substance (2) is emitted or light whose wavelength is changed is measured with respect to the intensity of the light at at least one frequency or with respect to the frequency shift, a corresponding measurement signal being output to an evaluation circuit associated with the spectrometer device (6), and

- The device has on its upper side or on its outer side a measuring surface section (11) which is adapted in shape and extent of the biologically active and / or biologically activatable substance (2) to be examined.

2. Device according to claim 1, characterized in that the biologically active and / or biologically activatable substance is a biological tissue, that is a human, animal or plant tissue.

3. Apparatus according to claim 1 or 2, characterized in that at least part of the optical light guide (4) and the sensor device (5) are housed in a housing (12), and on or in the top of the housing a measuring surface portion ( 11) comprehensive or at least partially correlated bearing surface portion (13) is formed or provided, on which a substance to be examined (2) corresponding body part of the subject, in particular a hand, a forearm or a foot or a leg is placed, said the Support surface portion (13) on or in the top of the housing (12) formed guide means (14) for aligning the on the support surface portion (12) to be deposited body part of the subject is provided.

4. The device according to claim 1, 2 or 3, characterized in that the optical light guide (4) has a light exit section (8), which forms a structural unit (9) with the sensor device (5), this building Liehe unit ( 9) on its upper side or outer side has the measuring surface section (11).

5. Device according to one of the preceding claims, characterized in that the guide device (14) by a on or in the top of the housing (12) provided, approximately medium finger wide recess (14) or thickening is formed.

6. Device according to one of the preceding claims, character- ized in that the surface of the measuring surface section (11) is approximately convexly curved and formed substantially following the contours of a slightly clenched hand (2), or the surface of the measuring surface section (11) strong convexly curved and formed substantially following the contours of a clenched hand.

7. Device according to one of the preceding claims, characterized in that on the measuring surface portion (11) or in the immediate vicinity of an image display device is formed.

8. Device according to one of the preceding claims, characterized in that the measuring surface section (11) is provided or formed on or on a measuring head, and the measuring head is connected via the optical light guide with the light source.

9. Device according to one of the preceding claims, characterized in that all optical and / or optoelectronic components, that is, the light source (3), the optical light guide (4), the sensor device (5), and the

Spectrometer means (6) are housed in the housing (12).

10. Device according to one of the preceding claims, characterized in that the sensor device (5) associated with optical or optoelectronic spectrometer means (6) comprises a semiconductor sensor device which has at least one avalanche photodiode with a semiconductor gate, which of the frequency to be measured or Freqenzver- shift equivalent.

11. The device according to claim 10, characterized in that the semiconductor sensor device has a variable with respect to the measuring frequency and / or tunable frequency gap.

12. A method for optical examination and evaluation of a biologically active and / or biologically activatable substance (2) by the application of infrared, visible or ultraviolet light, in which the substance under examination is optically excited so that it either emits light itself (in particular fluorescence analysis) or the wavelength of the applied light changes (in particular Raman analysis), the method comprising the steps:

Irradiating the substance to be examined with a light emitted by a light source (3) which is supplied by means of an optical light guide (4) to the substance (2) to be examined,

Detecting the radiation emitted or changed by the substance (2) by means of an optical or optoelectronic sensor device (5) assigned to the substance (2) to be examined,

Measurement of the light emitted by the substance (2) or changed in its wavelength with regard to the intensity of the light at at least one frequency or with respect to the frequency shift by means of an optical or optoelectronic spectrometer device (6) assigned to the sensor device (5)

Output of a corresponding measurement signal to an evaluation circuit.

13. The method according to claim 12, characterized in that the biologically active and / or biologically activatable substance is a biological tissue, that is a human, animal or plant tissue.

14. The method according to claim 12 or 13, characterized in that at least part of the optical light guide (4) and the sensor device (5) are housed in a housing (12), and on or in the top of the housing a measuring surface portion ( 11) comprehensive or at least partially correlated bearing surface portion (13) is formed or provided on which a the substance to be examined (2) corresponding body part of the subject, in particular a hand, a forearm or a foot or a leg is placed, wherein the support surface section (13) has a guide device (14) formed on or in the upper side of the housing (12) for aligning the support surface with the support surface. surface portion (12) to be deposited body part of the subject is provided.

15. The method according to any one of the preceding claims, characterized in that by applying or applying the biologically active and / or biologically activatable substance (2) to the sensor device (5) a plurality of substances capable of fluorescence n, m (n, m = a, b, c, d, ...) in the substance are excited by a light pulse emitted by the light source (3), and these substances (a, b, c, d, ...) in response thereto itself light signals of a certain wavelength and in a certain intensity (I _a , I _{b /} I _c , I _d , etc.) emit, these light signals (I _a , I _b , I _c , I _d , etc.) are measured.

16. The method according to claim 15, characterized in that from the measured intensity values (I _a , I _b , I _c , I _d ) of the light signals a plurality, at least three or four, in particular at least five or six different metabolic parameters S _n (with n = a, b, c, d, ...), where:

S _n = F (I _n , λ ") X G (I _n , λ _m )

where F and G are two different mathematical functions of intensities and wavelengths, with n, m = a, b, c, d, ..., and n ≠ m; and the correlation or mathematical combination X of the two functions F and G in the simplest form is a product or a sum, in the form:

S _n = π [F (I _n , λ _n ) G (I _m , λ _m )] or

S _n = Σ [F (I _n , λ ")] G (I _m , λ _m )],

with n, m = a, b, c, d, ..., and n ≠ m, or n = m.

17. Method according to claim 15, characterized in that the substances n, m with their measured emission wavelengths (λ _n , λ _m ) and their measured intensities (I _n , I _m ) have in particular the following biochemical substances:

a = ATP (adenosine triphosphate), and / or b = GTP (guanosine triphosphate), and / or c = FAD (flavin adenine dinucleotide), and / or d = NADH (nicotinamide adenine dinucleotide reduced), and / or e = NADP (nicotinamide adenine dinucleotide phosphate), and / or f = kynurenine, and / or g = orotic acid, and / or h = thromboxane, and / or i = tryptophan.

18. The method according to any one of claims 15 to 17, characterized in that the fluorescence intensities (I _n , I _m ) in the wavelength range (λ _n , λ _m ) of 287 nm to 800 nm, preferably from 340 nm to 600 nm, for the Substances n, m = a, b, c, d, ... are measured.

19. The method according to any one of claims 15 to 18, characterized in that the measurement of the fluorescence intensities (I _n , I _m ) each at a defined time (t _n , t _m ) and / or at defined time intervals (.DELTA.t _n , .DELTA.t _ra ), where n ≠ mt _n ≠ t _m Δt "≠ At - _n m

20. The method according to any one of claims 15 to 19, characterized in that at a defined time (t _n , t _m ) of the measurement, a mental or physical stress of the patient takes place, and the fluorescence intensities (I _n , I _m ) before and after the load are measured several times and the regulatory process is determined in the metabolism.

21. The method according to any one of the preceding claims, characterized in that from the optical examination or analysis of the biologically active and / or biologically activatable substance and from the measurement of the metabolic parameters S _n (with n = a, b, c, d, .. .) several different specific state variables Z _{n are} calculated as mathematical functions of the metabolic parameters S _n and graphically represented, these specific state variables Z _n having the following:

α = cell division activity, and / or β = metabolic activity, and / or

Y = activity of biosyntheses, and / or δ = regulation of immune functions, and / or ε = inflammatory processes, and / or ζ = energy turnover, and / or η = energy consumption for cell division activity, and / or θ = regulated and unregulated cell regeneration, and / or ξ = inflammatory regulated cell regeneration processes, and / or p = risk parameters of damage to health, and / or σ = activated tissue regeneration, and / or φ = complex metabolic characteristics, and / or χ = redox equivalent, and / or ψ = mental stability parameter.

22. The method according to any one of claims 16 to 21, characterized in that the biologically active substances which exhibit an autofluorescence are excited to emission in the cellular and intercellular area with light having an excitation wavelength of 287 nm to 340 nm, preferably 340 nm ,

23. Method according to one of the preceding claims, characterized in that the method is used for the noninvasive examination of control and regulating processes of human and animal metabolism, and / or for the diagnosis of diseases and preventive examinations, and / or for roughnecks. tine examinations by occupational groups and athletes with high physical and psychological stress, and / or for therapy control, and / or the course of dialysis and Aphere- sebehandlung and to determine the Antioxidantienbedarfs is applied.